Báo cáo khoa học: "Target splitting in radiation therapy for lung cancer: further developments and exemplary treatment plans" pps

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Radiation Oncology
Open Access
Research
Target splitting in radiation therapy for lung cancer: further
developments and exemplary treatment plans
Karl Wurstbauer*, Heinz Deutschmann, Peter Kopp, Florian Merz,
Helmut Schöller and Felix Sedlmayer
Address: Department of Radiation Oncology and radART – Institute for Research and Development on Advanced Radiation Technologies at the
Paracelsus Medical University, Salzburg, Austria
Email: Karl Wurstbauer* - ; Heinz Deutschmann - ; Peter Kopp - ;
Florian Merz - ; Helmut Schöller - ; Felix Sedlmayer -
* Corresponding author
Abstract
Background: Reporting further developments evolved since the first report about this conformal
technique.
Methods: Technical progress focused on optimization of the quality assurance (QA) program,
especially regarding the required work input; and on optimization of beam arrangements.
Results: Besides performing the regular QA program, additional time consuming dosimetric
measurements and verifications no longer have to be accomplished.
'Class solutions' of treatment plans for six patients with non-resected non-small cell lung cancer in
locally advanced stages are presented. Target configurations comprise one central and five
peripheral tumor sites with different topographic positions to hilus and mediastinum. The mean
dose to the primary tumor is 81,9 Gy (range 79,2–90,0 Gy), to macroscopically involved nodes 61,2
Gy (range 55,8–63,0 Gy), to electively treated nodes 45,0 Gy. Treatments are performed twice
daily, with fractional doses of 1,8 Gy at an interval of 11 hours. Median overall treatment time is 33
days. The set-up time at the linac does not exceed the average time for any other patient.
Conclusion: Target splitting is a highly conformal and nonetheless non-expensive method with
regard to linac and staff time. It enables secure accelerated high-dose treatments of patients with

NSCLC.
Background
In order to improve locoregional tumor control of lung
cancer patients by radiation therapy, raising of the tumor
dose is mandatory. This constitutes a challenge to be over-
come only by the use of conformal, healthy tissue sparing
techniques. Following rather simple 3D approaches,
sophisticated forms of intensity modulated techniques
such as tomotherapy, intensity modulated arc therapies or
volumetric modulated arc therapies have been described
recently and begin to be applied clinically [1,2]. Results of
treatments of lung cancer patients with these latter tech-
niques are still missing.
In 1999 our first report about the conformal technique of
target splitting in external radiotherapy of lung cancer has
been published [3]. Since then, we use this method rou-
Published: 14 August 2009
Radiation Oncology 2009, 4:30 doi:10.1186/1748-717X-4-30
Received: 20 May 2009
Accepted: 14 August 2009
This article is available from: />© 2009 Wurstbauer et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( />),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Radiation Oncology 2009, 4:30 />Page 2 of 10
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tinely for lung cancer patients in all stages. During the past
years, this technique has continuously been evolved with
regard to optimizing the procedures for quality assurance
and raising conformity of the treatment plans.
This report gives an update about the technical innova-

tions and implications for workflow and demonstrates
exemplary treatment solutions in 6 lung cancer patients
with different tumor topographies (Figure 1, Figure 2, Fig-
ure 3, Figure 4, Figure 5 and Figure 6).
Methods
The technique of target splitting has been described in
detail [3]. In an individually chosen transversal plane, the
target is split into a cranial and a caudal part. For either
part completely independent beam arrangements are
designed. Half collimated, coplanar asymmetric fields
('half beams'), in general each adjacent to the isocentric
splitting (junction) plane, allow for set-up of highly con-
formal treatment plans.
Progress in Quality Assurance (QA) since the first report
In order to prevent over- or underdosages in or next to the
junction plane, special care has to be taken to ensure cor-
rect positioning of independent jaws at the central axis. As
an individual fine adjustment of MLC jaws for each
patient is time consuming, we developed and imple-
mented a QA program which is periodically testing for
over- or underdosages by means of amorphous silicon flat
panel imaging (EPID). Because different collimator rota-
tions (0°, ± 90°) will be applied in clinical cases for opti-
mal MLC coverage and/or to allow the insertion of a
motorized wedge, all combinations of possibly adjacent
jaws (x1/x2, x1/y1, x1/y2, y1/x2 and y1/y2) have to be
tested. On a monthly basis and after each head mainte-
nance, five different sequences of beam segments are irra-
Centrally located tumorFigure 1
Centrally located tumor. 83 years; central squamous cell carcinoma, 4 cm ∅, atelectasis upper lobe, paralysis phrenical

nerve with elevated diaphragma; enlarged PET-positive ipsilateral mediastinal nodes. A. Scheme; position of junction plane and
upper and lower borders, doses (Gy). B. Treatment plan single fraction. C. Overall treatment plan. D. DVHs.
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diated onto the panel: the first four sequences deliver each
one quadrant field with four intersegmental collimator
rotations (0°, 90°, 180°, -90°) to be summed up in one
image per sequence. The last sequence keeps the collima-
tor rotation at 0°, while irradiating the four quadrants by
changing the jaw- (and leave) positions (Figure 7).
This method inherently guarantees that all jaw-offsets will
be aligned to the radiation field's central axis as defined by
the mechanical axis of collimator rotation. If over- or
underdosages are measured along the junction lines, a
straight forward calibration of jaw and leave positions
with sub-millimeter accuracy is possible, if the relation-
ship between maldosage and field-shift is known. The lat-
ter can easily be determined once in advance from single
jaw and MLC-leaf penumbra measurements. However, in
detail, the problem has some degree of complexity, since
the relative position of a leaf to the closely following
backup-jaw will influence the gradient of the penumbra as
well as inter-leave-leakage in the junction plane. Addi-
tionally, different penumbra gradients of x and y jaws
(due to their different distance to the focus of the
machine) will sum up to an unavoidable, slightly inhom-
geneous dose distribution apparent as parallel regions of
over- and underdosage next to the junction plane (Figure
7). Over- or underdosages in the range of up to 10%
within a zone of less than ± 1 mm can be neglected.

Although this error might be increased in principal by
connecting two opposing beams (knowing that the
machine's isocenter is a sphere or ellipsoid with radii in
Peripheral tumor, hilus/mediastinum to be treated not within the craniocaudal extension of the the primary tumorFigure 2
Peripheral tumor, hilus/mediastinum to be treated not within the craniocaudal extension of the the primary
tumor. 53 years; squamous cell carcinoma peripheral lower lobe, 5,5 cm ∅; enlarged PET-positive hilar, subcarineal and bilat-
eral mediastinal nodes. A. Scheme; position of junction plane and upper and lower borders, doses (Gy). B. Treatment plan sin-
gle fraction. C. Overall treatment plan. D. DVHs.
Radiation Oncology 2009, 4:30 />Page 4 of 10
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the range of 1 mm rather than a point), patient's daily
setup deviations and intrafractional respiratory move-
ments will blur the overall maldosage in the junction
plane as well as distributed gantry- and collimator angles,
which has been shown in a series of phantom-film meas-
urements.
Patient set-up, planning procedure and treatment delivery
Six exemplary treatment plans which cover different target
volume constellations have been chosen among patients
with advanced-stage NSCLC treated in the past three
years. All six patients participate in a prospective study, in
which the dose to the primary tumor is correlated to its
size [4]. Two patients are staged T2N2 and T2N3, respec-
tively; one patient T3N2 and T4N2, respectively.
Patients are set up in vacuum cradles, usually supine with
the hands above the head. A planning CT in treatment
position is performed as 'slow CT' from the apex to the
bases of the lung, patients freely breathing (non-spiral CT;
4 s/slice; slice thickness 7 mm formerly, more recently 5
mm; couch movements 8 mm or 5 mm) [5]. In the case of

atelectasis 18-fluorodeoxyglucose positron emission tom-
ography (FDG-PET) is performed in treatment position
and the slices are matched with the planning CT. Margins
from gross tumor volume (GTV) to planning target vol-
ume (PTV) are 7 mm, regarding primary tumor, macro-
scopically involved lymph nodes and elective lymph node
stations, defined as the region about 5 to 6 cm cranial to
macroscopically involved nodes. In contouring of the
organs at risk, the GTV is excluded from the lung volume,
the heart is contoured from about 1 cm below the level
where the lower edge of the pulmonary trunk crosses the
median to the apex of the heart. Esophagus and spinal
cord are contoured in their entire thoracic length.
Peripheral tumor, hilus/mediastinum to be treated partially within the craniocaudal extension of the the primary tumorFigure 3
Peripheral tumor, hilus/mediastinum to be treated partially within the craniocaudal extension of the the pri-
mary tumor. 73 years; squamous cell carcinoma basal middle lobe, 4,2 cm ∅; enlarged PET-positive hilar and ipsilateral medi-
astinal nodes. A. Scheme; position of junction plane and upper and lower borders, doses (Gy). B. Treatment plan single
fraction. C. Overall treatment plan. D. DVHs.
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Planning is performed with a 3D-planning system
(Oncentra Masterplan), inhomogeneities are taken into
account by a pencil beam algorithm. Dose constraints for
the spinal cord were set at 45 Gy, V20 (volume receiving
>20 Gy) for a single lung at 50%, V25 for both lungs con-
sidered as a single organ at 30%, the maximal dose to the
esophagus at 80 Gy (measured in the center of the esopha-
gus at its most exposed level).
Treatments were delivered with 15 MV photons, fractional
doses of 1,8 Gy (ICRU), twice daily, interval 11 h.

Since 2006, daily image guidance (IGRT) was performed
by MV cone beam CTs, since 2007 by orthogonal kV-
imaging with adjustment to the esophageal and large air-
ways' structures [6].
Results
In contrast to our previous report about this technique,
besides performing the regular QA program as described,
no additional time consuming dosimetric verifications
have to be accomplished.
For all 6 patients treatment plans with one single isocenter
can be provided. This enables a remote control of all treat-
ment steps by assisted setup functions. The daily set-up
time at the linac does not exceed the average time for any
other patient.
1. Centrally located tumor (Figure 1)
The junction plane is chosen above the central tumor. The
upper volume is treated by anterior-posterior (a-p) – right
oblique anterior and left oblique anterior, partially
wedged beams (290°, 0°, 70°), the lower volume by left
oblique anterior, left lateral and left oblique posterior,
partially wedged beams (25°, 90°, 165°). After 45 Gy
(elective dose for not macroscopically involved nodes)
the upper jaws of the upper volume are closed asymmet-
rically for a length of 5 cm. After 55,8 Gy (dose for macro-
scopically involved nodes) the primary tumor is boosted
to 79,2 Gy (excluding the nodes by setting of MLCs). V20
Peripheral tumor located lateral and distant to hilus/mediastinumFigure 4
Peripheral tumor located lateral and distant to hilus/mediastinum. 48 years; squamous cell carcinoma peripheral
upper lobe, 4 cm ∅; enlarged PET-positive hilar and ipsilateral mediastinal nodes. A. Scheme; position of junction plane and
upper and lower borders, doses (Gy). B. Treatment plan single fraction. C. Treatment plan single fraction of boost to primary

tumor. D. Overall treatment plan. E. DVHs.
Radiation Oncology 2009, 4:30 />Page 6 of 10
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of the right lung is 43%, of the left lung 32%, V25 for both
lungs 28%. In the upper volume the esophagus can be
spared very well; in the lower volume, because the pri-
mary tumor is partially directly adherent to the esopha-
gus, for about 3 cm it receives the full tumor dose at a
major part of its circumference.
2. Peripheral tumor, hilus/mediastinum to be treated not
within the craniocaudal extension of the the primary
tumor (Figure 2)
The junction plane is chosen above the primary tumor,
below the hilus. The upper volume is treated by 3 partially
wedged, left-sided beams (20°, 90°, 160°) to 59,4 Gy;
after 45 Gy the upper jaws are retracted asymmetrically for
5,5 cm. The lower volume (primary tumor) is treated with
three partially wedged right-sided beams (320°, 280°,
220°) to 84,6 Gy. V20 right and left lung and V25 both
lungs is 37%, 26% and 27%, respectively. V50 for the
heart is 2%.
3. Peripheral tumor, hilus/mediastinum to be treated
partially within the craniocaudal extension of the the
primary tumor (Figure 3)
The junction plane is chosen above the primary tumor.
The upper volume (hilus and mediastinum) is treated by
three, partially wedged fields (20°, 80°, 150°) to 61,2 Gy.
After 45,0 Gy the upper volume is reduced cranially for 6
cm. In the lower volume, the primary tumor is treated by
three, partially wedged fields (290°, 345°, 50°); only one

of these fields (345°) meets also the PTV of the nodes, sit-
uated only in the upper 2 cm of the caudal volume; the
missing dose is supplied by two partially wedged fields
(45°, 115°), which do not interfere grossly with the PTV
of the primary tumor. After 61,2 Gy these two fields are
Peripheral tumor located lateral, but close to hilus/mediastinumFigure 5
Peripheral tumor located lateral, but close to hilus/mediastinum. 67 years; adenocarcinoma peripheral upper lobe,
3,5 cm ∅; enlarged hilar nodes, mediastinoscopically proven bilateral mediastinal nodes. A. Scheme; position of junction plane
and upper and lower borders, doses (Gy). B. Treatment plan single fraction. C. Treatment plan single fraction of boost to pri-
mary tumor. D. Overall treatment plan. E. DVHs.
Radiation Oncology 2009, 4:30 />Page 7 of 10
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withdrawn and the primary tumor alone is treated to 79,2
Gy. V20 right and left lung and V25 both lungs is 49%,
22% and 26%, respectively. V50 for the heart is 2%.
4. Peripheral tumor located lateral and distant to hilus/
mediastinum (Figure 4)
The junction plane is chosen above the primary tumor.
The upper volume (elective nodes only) is treated by
three, partially wedged beams (305°, 0°, 55°) to 45 Gy.
Within the lower volume, the primary tumor is treated by
four, partially wedged fields (35°, 120°, 180°, 300°).
Two of these fields (120°, 300°) meet also the PTV of the
nodes, the missing dose to the nodes is added by two
fields, which do not interfere with the primary tumor.
After 63,0 Gy the primary tumor alone is boosted to 79,2
Gy. V20 left and right lung, V25 both lungs is 47%, 16%
and 26%, respectively. In the upper volume the esophagus
could have been better spared chosing a less steep angle
for the oblique beams (e.g. 285° and 75° instead of 305°

and 55°). However, as the whole upper volume is treated
only with an elective dose (45 Gy), significant esophageal
side effects have not been observed, and the beam angles
were optimized with regard to sparing of lung tissues. In
the lower volume the esophagus can be spared fairly.
D(max) for the heart is 3,5 Gy.
5. Peripheral tumor located lateral, but close to hilus/
mediastinum (Figure 5). Junction plane above the primary
tumor
The isocenter is set in the center of the primary tumor,
which is treated by a rotational arc (345° to 180°) and a
right sided field (250°). The missing dose to the hilus and
mediastinum is added by two partially wedged fields
(335°, 170°). After the dose to the nodes is reached (59,4
Gy), the primary tumor is boosted by an arrangement of
six fields (25°, 85°, 145°, 205°, 265°, 325°) to 79,2 Gy.
Peripheral tumor, junction plane set within the primary tumorFigure 6
Peripheral tumor, junction plane set within the primary tumor. 62 years; squamous cell carcinoma dorsal upper lobe
with infiltration of the chest wall, 6,5 cm ∅; enlarged PET-positive hilar and ipsilateral mediastinal nodes. A. Scheme; position of
junction plane and upper and lower borders, doses (Gy). B. Treatment plan single fraction. C. Treatment plan single fraction of
boost to primary tumor. D. Overall treatment plan. E. DVHs.
Radiation Oncology 2009, 4:30 />Page 8 of 10
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Due to histological proof of bilaterally positive nodes in
the middle mediastinum, the whole upper mediastinum
has been electively irradiated up to 45 Gy (by three par-
tially wedged fields; 290°, 0°, 70°). V20 left and right
lung, V25 both lungs: 52%, 32% and 32%, respectively.
D(max) to the heart: 5 Gy.
6. Peripheral tumor, junction plane set within the primary

tumor (Figure 6)
In order to optimize the angles of the beam arrangements
the junction plane is set within the primary tumor. The
upper volume is treated by oblique opposing plus left
oblique beams (25°, 125°, 205°), with good sparing of
spinal cord and esophagus, at the cost of some medial
parts of the right lung. In the caudal volume, the oblique
ventral beam can be taken less steep (40°, 125°, 200°),
resulting in a better sparing of the lung while maintaining
good sparing of myelon and esophagus,. This series is
treated to 63,0 Gy; after 45 Gy the elective nodes of the
upper mediastinum are withdrawn by setting of MLCs. In
a second series the primary tumor is boosted to 90,0 Gy
(130°, 180°, 250°). V20 right and left lung and V25 both
lungs is 37%, 19% and 25%, respectively. D(max) for the
heart is 6 Gy.
The mean dose to the primary tumor of these six patients
amounts to 81,9 Gy (79,2 – 90,0 Gy), to macroscopically
involved nodes 61,2 Gy (55,8 – 63,0 Gy), and to elective
nodes 45,0 Gy in an accelerated fractionation schedule.
The median overall treatment time was 33 days (31 – 38
days).
Discussion
In primary radiation therapy of NSCLC a positive dose-
response relationship with regard to tumor control and
survival seems to be proven [7,8]. Furthermore, in order
to prevent accelerated repopulation of clonogenic tumor
cells, a short overall treatment time is important [9,10]. In
this study we present exemplary treatment plans of
patients with different topographical realities, in which

doses up to 90,0 Gy in 33 days have been safely applied.
Thereby beam arrangements are shown, which to our
knowledge have not been published previously.
In 1979 Williamson first described the matching of
orthogonal fields by an isocentric half-beam technique,
using a large lead block positioned in the accessory tray at
the beam axis [11]. He proposed this method for head
and neck, breast and craniospinal treatments. With the
availability of independently moving jaws asymmetric
collimators were used to split the beam for head and neck
patients [12]. In 1999, in our previous report we proposed
this technique not only for matching orthogonal fields,
but to perform completely independent planning and
treatments on both sides of the junction plane, including
rotational elements, static fields at arbitrary angles, wedge
filters, etc. [3]. We called this technique 'target splitting',
because the positioning of the junction plane depends on
shape and topographic parameters of the target and its
surroundings.
The method was initially applied to lung cancer patients.
With ongoing practice some 'rules' evolved, breaking
some former "taboos" in radiotherapy of lung cancer:
1. Minimizing the dose to the ipsilateral (i.e. tumor
bearing) lung.
In many cases the ipsilateral lung will be the first organ
to reach the dose constraint. This can be avoided by
setting beams via median structures (spine, anterior
mediastinum), mostly angled to the contralateral lung
(e.g. caudal volume of patient 1). The contralateral
lung is irradiated if necessary to its tolerance limit.

2. If necessary, for optimizing beam arrangements
junction planes can easily be set within the primary
tumor itself (e.g. patient 6) or within macroscopically
involved nodes (e.g. patient 1, 4, 6) (comments
below).
As to elective nodal irradiation, usually the region about 5
– 6 cm above macroscopic nodal disease is included into
the PTV. If the upper mediastinal nodes are involved, a
supraclavicular field is used. Most studies engaged in dose
escalation of NSCLC disapprove elective nodal irradia-
tion, in order to gain potential to raise the dose to the pri-
mary tumor [8,13]. However, isolated elective nodal
recurrence occurs. Rosenzweig et al describe an actuarial
elective nodal failure rate at 2 years in locally controlled
patients of 9% [14]. RTOG 9311, also omitting elective
Dosimetric verification of accuracy of field junctions of a MLC headFigure 7
Dosimetric verification of accuracy of field junctions
of a MLC head. White and black levelled regions represent
dose inhomogeneities below 10%. Left: One double half colli-
mated quadrant beam (45°) was irradiated 4 times with rela-
tive intersegmental collimator rotations of 0°(I), +90°(II),
+180°(III), -90°(IV). Right: 4 segments, each irradiated in dif-
ferent quadrants (I-IV) by changing the field aperture with a
fixed collimator rotation (45°).
Radiation Oncology 2009, 4:30 />Page 9 of 10
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nodal irradiation, reports 12/176 patients with isolated
elective nodal recurrences [13]. Microscopic spread cra-
nial to macroscopically involved nodes must be assumed
in a relevant portion of patients and a 'collateral' dose

from the macroscopic PTVs in these sites is not applied.
Because FDG-PET scans detect malignant tissue only at a
minimal size of about 0,5 cm, this mode has been
retained unchanged also with the availability of PET stag-
ing. In our experience of treating >100 patients with 45 Gy
in 2,5 weeks, no isolated recurrence in electively treated
sites until now has been observed.
Regarding pulmonary doses, when we started to imple-
ment target splitting and to raise the dose, we set the con-
straints as recommended for safe 3D-treatments some
years ago: a dose of ≥ 20 Gy should not exceed 50% of the
volume of a single lung and ≥ 25 Gy should not exceed
30% of the volume of both lungs together [15-17].
Observing these limits resulted in a high tolerability using
the target splitting technique. However, patients with pre-
existing lung fibrosis should be excluded from acceler-
ated, high dose therapies [4]. With regard to the
esophagus we limited the maximum dose in accelerated
schedules to 80 Gy. Such a high dose rarely must be
applied because the esophageal dose mostly is deter-
mined by the dose given to the nodes, not to the primary
tumor and because target splitting has a capability also to
spare the esophagus. In our experience of 15 years with
high dose treatments of lung cancer patients we did not
observe any severe late esophageal toxicity [4,18,19].
To account for sufficient margins, a rim of 7 mm from
GTV to PTV in patients freely breathing might appear
rather tight. This issue has been described and discussed
in detail previously [5]. Shortly, slow planning CTs depict
the different relevant positions of the moving tumors

individually, so that adding a general extra-margin for
tumor motion (internal margin) is not necessary. Further-
more, we consider a margin for microscopic spread from
GTV to the clinical target volume (CTV) in high dose radi-
otherapy dispensable. Giraud et al report 95% of micro-
scopic tumor spread within a distance of 8 and 6 mm
from the gross tumor in adenocarcinomas and squamous
cell carcinomas of the lung, respectively [20]. Applied to
the presented six patients' gross tumor dose of 81,9 Gy a
sufficient dose to the rim of microscopic disease (about 45
Gy in 2,5 weeks) is delivered anyway.
It has been criticized that 4D planning CTs depict more
exactly the extreme positions of moving tumors and
deliver sharper contours compared to slow CTs. Perhaps
this is also a question of institutional practice and habits.
Not capturing extreme, short lasting positions of parts of
the tumor can be advantageous, when a resulting smaller
PTV enables raising the total dose. Also, in handling with
somewhat blurred contours drawing the PTV, with some
practice we don't see any problem. Summing up, we con-
sider slow planning CTs a simple, effective, non-expensive
method, capable to depict the relevant positions of a mov-
ing lung tumor.
The issue of setting the junction plane within macroscopic
disease has been discussed in our previous report [3]. In
the phantom a homogeneously irradiated volume is
proven. Actually, with non-splitting techniques there is
the same situation: to the patient is offered a homogene-
ously treated volume. Also, intensity modulated treat-
ments use a multitude of single static and/or dynamic

elements resulting in homogeneously treated volumes.
Our planning system facilitates a pencil beam algorithm.
More advanced algorithms such as superposition-convo-
lution methods would compute the influence of inhomo-
geneities on dose distributions more accurately, but this
seems to be negligible for the aim of this report.
Target splitting has first enabled the secure application of
doses up to 94,5 Gy with conventional fractionation for
NSCLC patients [18]. After a phase I/II trial, showing good
tolerability of accelerated, twice daily applied high dose
radiotherapy in 30 patients, currently a prospective accel-
erated high dose trial is ongoing, relating the dose to the
size of the primary tumors (4 groups: <2,5 cm/73,8 Gy;
2,5–4,5 cm/79,2 Gy; 4,5–6,0 cm/84,6 Gy; >6,0 cm/90,0
Gy; 1,8 Gy bid). The first results in 102 patients show an
actuarial local tumor control at 2 years of 82% and an
encouraging median overall survival time of 28,0 months
[4,19]. Recently, sophisticated forms of intensity modu-
lated techniques such as tomotherapy, intensity modu-
lated arc therapies or volumetric modulated arc therapies
have been described [1,2]. As results of treatments of lung
cancer patients with these techniques are still missing, a
comparison of the efficacy of the different approaches is
not yet possible.
Recently, a shift in the incidence from central to periph-
eral tumors in lung cancer patients has been observed
[21]. With its ability to differentiate the beam arrange-
ments, the technique of target splitting seems to be a use-
ful tool especially for peripheral tumors in advanced
stages.

With growing incidence we use this technique also for
extrathoracic tumor sites, such as thyroid, stomach, pel-
vic/paraaortic, limbs etc.
Summarizing, the technical developments of target split-
ting evolved since the first report enable secure dose esca-
lations above 90 Gy for patients with advanced NSCLC,
without heavy inroad on resources in term of staff and
linac time.
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Competing interests
The authors declare that they have no competing interests.
Authors' contributions
KW mainly conceived and drafted the manuscript, partic-
ipated in the conception of target splitting; HD conceived
the QA program, drafted its description in the manuscript
and gave substantial support in the development of target
splitting; PK, FM and HS acquired the data and drafted the

figures; FS gave final approval of the version to be pub-
lished. All authors read and approved the final manu-
script.
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